Tat-Biliverdin Reductase A Exerts a Protective Role in Oxidative Stress-Induced Hippocampal Neuronal Cell Damage by Regulating the Apoptosis and MAPK Signaling

Tat-Biliverdin Reductase A Exerts a Protective Role in Oxidative Stress-Induced Hippocampal Neuronal Cell Damage by Regulating the Apoptosis and MAPK Signaling

Reactive oxygen species (ROS) is major risk factor in neuronal diseases including ischemia. Although biliverdin reductase A (BLVRA) plays a pivotal role in cell survival via its antioxidant function, its role in hippocampal neuronal (HT-22) cells and animal ischemic injury is not clearly understood...

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Main Authors: Sang Jin Kim, Min Jea Shin, Dae Won Kim, Hyeon Ji Yeo, Eun Ji Yeo, Yeon Joo Choi, Eun Jeong Sohn, Kyu Hyung Han, Jinseu Park, Keun Wook Lee, Jong Kook Park, Yong-Jun Cho, Duk-Soo Kim, Won Sik Eum, Soo Young Choi
Format: Article
Language:English
Published: MDPI AG 2020-04-01
Series:International Journal of Molecular Sciences
Subjects:
Tat-BLVRA
oxidative stress
MAPK
ischemic injury
protein therapy
Online Access:https://www.mdpi.com/1422-0067/21/8/2672
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spelling doaj-7eab787437aa4d019bf83ec6ec95de6f2020-11-25T02:23:40ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-04-01212672267210.3390/ijms21082672Tat-Biliverdin Reductase A Exerts a Protective Role in Oxidative Stress-Induced Hippocampal Neuronal Cell Damage by Regulating the Apoptosis and MAPK SignalingSang Jin Kim0Min Jea Shin1Dae Won Kim2Hyeon Ji Yeo3Eun Ji Yeo4Yeon Joo Choi5Eun Jeong Sohn6Kyu Hyung Han7Jinseu Park8Keun Wook Lee9Jong Kook Park10Yong-Jun Cho11Duk-Soo Kim12Won Sik Eum13Soo Young Choi14Department of Biomedical Science and Research, Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, KoreaDepartment of Biomedical Science and Research, Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, KoreaDepartment of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Gangneung-Wonju National University, Gangneung 25457, KoreaDepartment of Biomedical Science and Research, Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, KoreaDepartment of Biomedical Science and Research, Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, KoreaDepartment of Biomedical Science and Research, Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, KoreaDepartment of Biomedical Science and Research, Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, KoreaDepartment of Biomedical Science and Research, Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, KoreaDepartment of Biomedical Science and Research, Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, KoreaDepartment of Biomedical Science and Research, Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, KoreaDepartment of Biomedical Science and Research, Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, KoreaDepartment of Neurosurgery, Hallym University Medical Center, Chuncheon 24253, KoreaDepartment of Anatomy, College of Medicine, Soonchunhyang University, Cheonan-Si 31538, KoreaDepartment of Biomedical Science and Research, Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, KoreaDepartment of Biomedical Science and Research, Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, KoreaReactive oxygen species (ROS) is major risk factor in neuronal diseases including ischemia. Although biliverdin reductase A (BLVRA) plays a pivotal role in cell survival via its antioxidant function, its role in hippocampal neuronal (HT-22) cells and animal ischemic injury is not clearly understood yet. In this study, the effects of transducible fusion protein Tat-BLVRA on H<sub>2</sub>O<sub>2</sub>-induced HT-22 cell death and in an animal ischemia model were investigated. Transduced Tat-BLVRA markedly inhibited cell death, DNA fragmentation, and generation of ROS. Transduced Tat-BLVRA inhibited the apoptosis and mitogen activated protein kinase (MAPK) signaling pathway and it passed through the blood-brain barrier (BBB) and significantly prevented hippocampal cell death in an ischemic model. These results suggest that Tat-BLVRA provides a possibility as a therapeutic molecule for ischemia.https://www.mdpi.com/1422-0067/21/8/2672Tat-BLVRAoxidative stressMAPKischemic injuryprotein therapy
collection DOAJ
language English
format Article
sources DOAJ
author Sang Jin Kim
Min Jea Shin
Dae Won Kim
Hyeon Ji Yeo
Eun Ji Yeo
Yeon Joo Choi
Eun Jeong Sohn
Kyu Hyung Han
Jinseu Park
Keun Wook Lee
Jong Kook Park
Yong-Jun Cho
Duk-Soo Kim
Won Sik Eum
Soo Young Choi
spellingShingle Sang Jin Kim
Min Jea Shin
Dae Won Kim
Hyeon Ji Yeo
Eun Ji Yeo
Yeon Joo Choi
Eun Jeong Sohn
Kyu Hyung Han
Jinseu Park
Keun Wook Lee
Jong Kook Park
Yong-Jun Cho
Duk-Soo Kim
Won Sik Eum
Soo Young Choi
Tat-Biliverdin Reductase A Exerts a Protective Role in Oxidative Stress-Induced Hippocampal Neuronal Cell Damage by Regulating the Apoptosis and MAPK Signaling
International Journal of Molecular Sciences
Tat-BLVRA
oxidative stress
MAPK
ischemic injury
protein therapy
author_facet Sang Jin Kim
Min Jea Shin
Dae Won Kim
Hyeon Ji Yeo
Eun Ji Yeo
Yeon Joo Choi
Eun Jeong Sohn
Kyu Hyung Han
Jinseu Park
Keun Wook Lee
Jong Kook Park
Yong-Jun Cho
Duk-Soo Kim
Won Sik Eum
Soo Young Choi
author_sort Sang Jin Kim
title Tat-Biliverdin Reductase A Exerts a Protective Role in Oxidative Stress-Induced Hippocampal Neuronal Cell Damage by Regulating the Apoptosis and MAPK Signaling
title_short Tat-Biliverdin Reductase A Exerts a Protective Role in Oxidative Stress-Induced Hippocampal Neuronal Cell Damage by Regulating the Apoptosis and MAPK Signaling
title_full Tat-Biliverdin Reductase A Exerts a Protective Role in Oxidative Stress-Induced Hippocampal Neuronal Cell Damage by Regulating the Apoptosis and MAPK Signaling
title_fullStr Tat-Biliverdin Reductase A Exerts a Protective Role in Oxidative Stress-Induced Hippocampal Neuronal Cell Damage by Regulating the Apoptosis and MAPK Signaling
title_full_unstemmed Tat-Biliverdin Reductase A Exerts a Protective Role in Oxidative Stress-Induced Hippocampal Neuronal Cell Damage by Regulating the Apoptosis and MAPK Signaling
title_sort tat-biliverdin reductase a exerts a protective role in oxidative stress-induced hippocampal neuronal cell damage by regulating the apoptosis and mapk signaling
publisher MDPI AG
series International Journal of Molecular Sciences
issn 1661-6596
1422-0067
publishDate 2020-04-01
description Reactive oxygen species (ROS) is major risk factor in neuronal diseases including ischemia. Although biliverdin reductase A (BLVRA) plays a pivotal role in cell survival via its antioxidant function, its role in hippocampal neuronal (HT-22) cells and animal ischemic injury is not clearly understood yet. In this study, the effects of transducible fusion protein Tat-BLVRA on H<sub>2</sub>O<sub>2</sub>-induced HT-22 cell death and in an animal ischemia model were investigated. Transduced Tat-BLVRA markedly inhibited cell death, DNA fragmentation, and generation of ROS. Transduced Tat-BLVRA inhibited the apoptosis and mitogen activated protein kinase (MAPK) signaling pathway and it passed through the blood-brain barrier (BBB) and significantly prevented hippocampal cell death in an ischemic model. These results suggest that Tat-BLVRA provides a possibility as a therapeutic molecule for ischemia.
topic Tat-BLVRA
oxidative stress
MAPK
ischemic injury
protein therapy
url https://www.mdpi.com/1422-0067/21/8/2672
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